Fast and catalyst-free cross-linking strategy is of great significance for construction of covalently cross-linked hydrogels. Here, we report the condensation reaction between o-phthalaldehyde (OPA) and N-nucleophiles (primary amine, hydrazide, and aminooxy) for hydrogel formation for the first time. When four-arm poly(ethylene glycol) (4aPEG) capped with OPA was mixed with various N-nucleophile-terminated 4aPEG as building blocks, hydrogels were formed with superfast gelation rate, high mechanical strength and markedly low critical gelation concentrations. Small molecule model reactions indicate the key to these cross-links is the fast formation of heterocycle phthalimidine product or isoindole (bis)hemiaminal intermediates, depending on the N-nucleophiles. The second-order rate constant for the formation of phthalimidine linkage (4.3 M⁻¹ s⁻¹) is over 3000-fold and 200-fold higher than those for acylhydrazone and oxime formation from benzaldehyde, respectively, and comparable to many cycloaddition click reactions. Based on the versatile OPA chemistry, various hydrogels can be readily prepared from naturally-derived polysaccharides, proteins or synthetic polymers without complicated chemical modification. Moreover, biofunctionality is facilely imparted to the hydrogels by introducing amine-bearing peptides via the reaction between OPA and amino group.

中文翻译：

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一种通过邻苯二甲醛缩合的快速通用交联策略，用于机械强化和功能性水凝胶

快速且无催化剂的交联策略对于构建共价交联水凝胶具有重要意义。在这里，我们首次报道了邻苯二甲醛(OPA) 和N-亲核试剂（伯胺、酰肼和氨氧基）之间的缩合反应形成水凝胶。当用 OPA 封端的四臂聚（乙二醇）（4aPEG）与各种N-亲核试剂封端的 4aPEG 作为构建块混合时，形成的水凝胶具有超快的凝胶速度、高机械强度和显着低的临界凝胶浓度。小分子模型反应表明这些交联的关键是杂环邻苯二甲酰亚胺产物或异吲哚（双）半胺中间体的快速形成，这取决于N- 亲核试剂。形成邻苯二甲酰亚胺键的二级速率常数 (4.3 M ^-1 s ^-1 ) 分别比从苯甲醛形成酰腙和肟的二级速率常数高 3000 倍和 200 倍，与许多环加成点击反应相当. 基于多功能的 OPA 化学，无需复杂的化学修饰，即可从天然来源的多糖、蛋白质或合成聚合物中轻松制备各种水凝胶。此外，通过OPA 和氨基之间的反应引入含胺的肽，可以轻松地将生物功能赋予水凝胶。